Connecting TDP-43 Pathology with Neuropathy.
Trends Neurosci
; 44(6): 424-440, 2021 06.
Article
en En
| MEDLINE
| ID: mdl-33832769
ABSTRACT
Transactive response DNA-binding protein 43 kDa (TDP-43), a multifunctional nucleic acid-binding protein, is a primary component of insoluble aggregates associated with several devastating nervous system disorders; mutations in TARDBP, its encoding gene, are a cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we review established and emerging roles of TDP-43 and consider how its dysfunction impinges on RNA homeostasis in the nervous system, thereby contributing to neural degeneration. Notably, improper splicing of the axonal growth-associated factor STMN2 has recently been connected to TDP-43 dysfunction, providing a mechanistic link between TDP-43 proteinopathies and neuropathy. This review highlights how a deep understanding of the function of TDP-43 in the brain might be leveraged to develop new targeted therapies for several neurological disorders.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Demencia Frontotemporal
/
Esclerosis Amiotrófica Lateral
Límite:
Humans
Idioma:
En
Revista:
Trends Neurosci
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos